WO1991014944A1 - A method for the collection of antibodies and the detection of a specific antibody species in a fluid sample and a device for carrying out said method as well as a kit comprising said device - Google Patents
A method for the collection of antibodies and the detection of a specific antibody species in a fluid sample and a device for carrying out said method as well as a kit comprising said device Download PDFInfo
- Publication number
- WO1991014944A1 WO1991014944A1 PCT/NL1991/000051 NL9100051W WO9114944A1 WO 1991014944 A1 WO1991014944 A1 WO 1991014944A1 NL 9100051 W NL9100051 W NL 9100051W WO 9114944 A1 WO9114944 A1 WO 9114944A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antibodies
- complex
- antigen
- membrane
- latex
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B10/0051—Devices for taking samples of body liquids for taking saliva or sputum samples
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/15—Devices for taking samples of blood
- A61B5/150007—Details
- A61B5/150343—Collection vessels for collecting blood samples from the skin surface, e.g. test tubes, cuvettes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54366—Apparatus specially adapted for solid-phase testing
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54366—Apparatus specially adapted for solid-phase testing
- G01N33/54386—Analytical elements
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56983—Viruses
- G01N33/56988—HIV or HTLV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B10/0064—Devices for taking samples of body liquids for taking sweat or sebum samples
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B10/007—Devices for taking samples of body liquids for taking urine samples
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B2010/0067—Tear or lachrymal fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/15—Devices for taking samples of blood
- A61B5/150007—Details
- A61B5/150015—Source of blood
- A61B5/15003—Source of blood for venous or arterial blood
Definitions
- This invention concerns a method for the collection of antibodies and the detection of a specific antibody species in a fluid sample and a device for carrying out said method as well as a kit comprising said device.
- European patent application 0200381 describes a solid phase system for use in a ligand-receptor assay for the detection of a selected analyte in a fluid sample comprising a porous matrix, wherein microspheres are entrapped, wherein said microspheres are bound with a receptor capable of capturing a specific target ligand.
- a receptor capable of capturing a specific target ligand.
- the solid phase according to EP-A-0200381 can consist of a membrane or filter made of glass fiber, nylon or ceramic material, wherein microspheres are entrapped, whereby said microspheres are made of a polymeric material such as for example latex that can bind to the receptor substance.
- a system is used here consisting of membrane-microspheres-immunological pair, whereby the pair consists of antibody-antigen or antigen-antibody.
- the method that is described in this EP-A comprises the application of a fluid sample on the solid phase system, whereby the receptor that is bound to the microspheres specifically binds the selected target ligand, as the fluid through passes the solid phase system.
- a solution of a receptor conjugate is adc d, whereby said conjugate is capable of specifically binding and labelling the target ligand in order for the bound target ligand to be detected on the solid phase.
- the term "receptor conjugate” is directed at a complex comprising a receptor and a label that can be detected. If the target ligand is an antigen the receptor conjugate can be a labelled antibody preferably a monoclonal antibody. On the other hand if the target ligand is an antibody labelled antigen can be used as receptor conjugate. Non-bound receptor conjugate can subsequently be removed by rinsing. The presence of bound receptor conjugate on the solid phase system implies the presence of the analyte in the sample.
- the EP-A also describes a device for carrying out such a method, whereby said device comprises the solid phase system as described, whereby said device is provided with means permitting the flow of a fluid sample through the solid phase system.
- protein A generally binds immunoglobulin and that it binds to Fc, it's constant region.
- Natural protein A is derived from Staphylococcus aureus. a pathogen, and is therefore not free of Staphylococcus toxins.
- American patent 4,189.466 describes the detection of the presence of rheumatoid factor (RF) in an animal sample by mixing the sample with a suspension of microbial cells containing protein A that have been sensitised with free Fc fragments of IgG for which RF is specific. If the mixing results in agglutination this indicates a positive result.
- RF rheumatoid factor
- Further protein A is coupled to for example agarose beads via chemically stable amide bonds and this complex is used in affinity chromatography for antibodies such as for example in American patent 4,879,211.
- DuPont has come on to the market with a recombinant protein A coupled to Sepharose, whereby said protein is expressed in E.coli, a non-pathogen rather than in the pathogen Staphylococcus aureus from which the natural protein A is obtained, which implies that the ligand is free of Staphylococcus toxins.
- DuPont uses recombinant protein A in the perflex 35RS affinity column. The molecule contains 5 homologous binding regions which are highly specific for the Fc portion of immunoglobulins.
- Immunoglobulin G is the major immunoglobulin which binds to recombinant protein A. Other immunoglobulins will also be adsorbed, however the class and sub-class specificity varies from species to species.
- the protein A can therefore be used for purifying IgG or for selectively removing IgG for analysis of the IG classes or for absorbing immunocomplexes for the purification of antigens.
- the method according to the invention is directed at a method for the collection of antibodies and the detection of a specific antibody species in a fluid sample comprising the steps of a) contacting said fluid sample with a solid phase matrix, said matrix comprising porous membrane, latex particles distributed in said porous membrane, recombinant protein A or G being covalently bound to said latex particles resulting in an aspecific binding of antibodies present in the fluid sample to form a complex [antibodies-protein A/G- latex-membranej, b) optionally removing excess fluid sample from said solid phase matrix, c) adding an antigen to said complex [antibodies-protein A/G- latex-membrane], said antigen being specific for the antibody species to be detected to allow formation of a complex containing said specific antibody species: [antigen-antibody-protein A/G-latex-membrane], d) optionally removing excess antigen from said porous matrix, e) using a detection method specific for the antigen of step c) .
- the antigens and antibodies that can be used with this method can be associated with bacteria, fungi, parasites or virus.
- a retrovirus such as for example a HIV-1 virus.
- This invention is directed at a new method for the collection of immunoglobulins from for example a body fluid for example for a diagnostic test.
- the invention is directed at the collection and detection of antibodies from body fluids of a mammal (including a human being) such as sweat, tears, blood, urine or preferably saliva. It is therefore possible to use body fluids in which the amounts of antibodies are low as fluid sample.
- the substance that can bind immunoglobulin is a recombinant protein G or recombinant protein A derived from E.coli or recombinant protein A and G and this protein is covalently bound to latex particles.
- These latex particles are surface modified for example by carboxylate, amide and/or hydroxy to enable them to bind protein (page 30, Uniform Latex Particles L.R. Bangs).
- the latex particles bound with protein G, A or G/A are entrapped in a porous membrane and form the solid phase matrix.
- the porous membrane can be made for example from cellulose, ceramic material, glass fiber, nylon or plastic.
- Polystyrene latex microparticles possess an intrinsic large surface which allows a large contact area for the immunoglobulin binding substance, recombinant protein A/G, and also for the sample fluid, resulting in a large amount of immunoglobulins that can be entrapped on the matrix, whereby the substrate for a very sensitive immunodiagnostic test is created.
- the matrix consisting of membrane-latex-protein A/G plays the part of collector of immunoglobulins and also serves as solid phase carrier for the identification of antibodies in an immunodiagnostic test. It is therefore only necessary to use one specifically binding antigen for the detection, in contrast to the test described in EP-A-0200381, whereby at least two specifically binding receptors of the analyte are necessary.
- a sample that is analysed according to the method of the invention can be examined for the presence of various specific antibodies by use of different solutions with specific antigens.
- the matrix used in the method according to the invention in which, in accordance with the antibody that is to be detected, a specific corresponding antigen is added after binding the antibodies and whereby the matrix is suited for the binding of every antibody.
- every possible antibody species that is present in the sample is bound and therefore every antibody can be detected by use of a specific antigen.
- The" specificity of this detection method depends on the antigen that is selected as means of detection.
- labelling with an enzyme it is possible to subsequently apply a substrate that brings about a colour change.
- a substrate for example 4-chloro-l-naphthol or TMB (tetramethylbenzidin) can be used as substrates.
- This invention is also directed at the use of a non-toxic, non-infectious complex of [recombinant protein A or G-latex-membrane] for immunological tests as well as a device for carrying out immunological tests according to the method of the invention.
- This device comprises a carrier containing the complex [protein A/G-latex- membrane].
- the carrier comprises an absorbent means incorporated in an elongated container with an opening at one end, whereby said end contains said complex and said opening enables the entrance of fluid via the complex absorbent means.
- the absorbent means is associated with the solid phase system complex in such a manner that the absorbent means draws fluid sample, that comes into contact with the solid phase system, through the complex.
- Said absorbent means can for example contain capillaries in a direction perpendicular to the surface over which the solid phase system is placed so that the capillaries are in direct communication with the pores of the solid phase system.
- FIG. 1 An embodiment of the device according to the invention is schematically illustrated in cross section in the drawing.
- FIG. 1 represents an elongated container of synthetic material provided with an opening at one end in which a membrane permeable for fluid 2 has been placed.
- Porous carrier 3 containing the complex [protein A or G-latex] is present under membrane 2 in the container 1.
- Carrier 3 is in contact with a fluid absorbing material 4 that can completely or partially fill the container 1.
- Various materials can be used as absorbent means such as cellulose acetate fibers, cotton, paper, plastic or polyester.
- the device can further for example be made of plastic with the following dimensions, a length of approximately 4- 14 cm, a depth of 1-5 mm and a width of 0,5-5 cm with an opening with a diameter of approximately 1-4 cm at one end.
- the absorbent means can have a length of 3-13 cm, a depth of 0,5-4,5 mm and a width of 0,3-4,5 cm.
- the open end of the device can be covered with a membrane
- a preferred embodiment of the device is a device whereby the open end of the device containing the substance that -is capable of binding immunoglobulin can be inserted into the mouth of a test person.
- the importance of the use of recombinant protein A without toxins that are present upon use of natural protein is an advantage.
- This is a new and extremely simple fast and handy method for collecting immunoglobulins G and the further use of said immunoglobulins in an immunodiagnostic test on a solid phase matrix. It is only necessary to keep the device in the mouth for the duration of 1 to 3 minutes. Saliva that comes into contact with the matrix passes through the latex particles bound with protein A, whereby the immunoglobulins that are present will bind quickly to protein A.
- the size and shape of the device make it simple to use and the discomfort of collecting blood or urine for an immunodiagnostic test is prevented.
- this same device in which the immunoglobulins are collected serves as carrier to be used in the identification of desired specific antibodies associated with a certain disease.
- an antigen of choice can be used to detect the specific antibodies from the collected saliva in an enzyme immunotest. An example of such a specific experiment in which saliva of a patient was collected is described below.
- a patient known to be HIV-1-antibody positive kept the device according to the invention under the tongue for 1 minute. After collecting the saliva 0.5 ml of a buffer containing PBS/0, 5% Tween- 20/2# BSA/0.01# Thimerosal with pH 7.8 was pipetted on to the membrane to rinse the excess proteins. After the buffer had been completely absorbed 0.2 ml of a HIV-1-solution containing 1 microgram of biotinilated protein recombinant envelope and core HIV-1 in PBS/0, 5% Tween-20/0.1% gelatine was added and also absorbed. The membrane was subsequently washed with 0.5 ml PBS/0.5% Tween-20/2% BSA/0.01J.
- the protein A/polystyrene microparticles were coupled covalently to each other in the following manner: latex particles were used that had been carboxylate modified (CML) with a diameter of 0.3*95 mm and are commercially available from CML.
- CML carboxylate modified
- the £-amino-N-caproic acid solution was made by dissolving 1 g £-amino-N-caproic acid in 0.5 molar potassium phosphate with pH 7 «4.
- the beads were resuspended in 3 ml of this solution. This was powerfully shaken on a vortex and incubated at room temperature in a mixer for 8 hours. After said 8 hours of incubation 0.3 ml of 1 molar ethanolamine was added to stop the reaction and the solution was incubated at room temperature for 1 hour: the beads were washed anoter three times in 10 ml of deionised water and centrifuged during ten minutes at 12,000 rpm.
- latex beads were resuspended in 2 ml of PBS and mixed vigorously. The mixture was sonified for 10 seconds and vortexed again. This procedure was repeated one more time. It is known that latex microparticles bind strongly to microporous glass fiber. The selection of glass fiber membrane should be made so that the latex particles can be incorporated in the pores of the membrane. In this example a Schleier and Schuell glass fiber membrane No. 3 ⁇ was used. The freshly prepared microparticles bound with protein A were dissolved 1:20 in PBS. 0.2 ml of diluted latex microparticles/protein A was pipetted in the shape of a cross onto the glass fiber membrane and allowed to dry at room temperature.
- the glass fiber membrane that contained latex-protein A-complex was blocked with a blocking buffer containing PBS/2 BSA/0.1 gelatine/0.5% Tween-20.
- a blocking buffer containing PBS/2 BSA/0.1 gelatine/0.5% Tween-20.
- the membrane was placed on an absorbent cushion/filter paper and 2 ml of the blocking buffer were added to the membrane in order for the buffer to be absorbed by the membrane so that an in depth blockage of the glass fiber matrix was accomplished.
- the matrix was allowed to dry at room temperature.
- the blocked matrix was stored before use in a plastic bag with a desiccator.
- These glass fiber-protein bound latex particles serve as solid matrix for collecting immunoglobulin in an increased concentration, which is obtained by a) the large surface area that is offered by the latex microparticles and b) the known high affinity of protein A for immunoglobulin G.
Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BR919105168A BR9105168A (en) | 1990-03-28 | 1991-03-27 | PROCESS FOR COLLECTING ANTIBODIES AND DETECTING A SPECIFIC ANTIBODY SPECIES IN A FLUID SAMPLE, NON TOXIC COMPLEX, NOT INFECTIOUS, DEVICE UNDERSTANDING A VEHICLE CONTAINING THE COMPLEX AND KIT TO IMMUNE DIAGNOSTIC DISEASES |
CA002056447A CA2056447A1 (en) | 1990-03-28 | 1991-03-27 | Method for the collection of antibodies and the detection of a specific antibody species in a fluid sample and a device for carrying out said method as well as a kit comprising said device |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NL9000735 | 1990-03-28 | ||
NL9000735 | 1990-03-28 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1991014944A1 true WO1991014944A1 (en) | 1991-10-03 |
Family
ID=19856834
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/NL1991/000051 WO1991014944A1 (en) | 1990-03-28 | 1991-03-27 | A method for the collection of antibodies and the detection of a specific antibody species in a fluid sample and a device for carrying out said method as well as a kit comprising said device |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0474858A1 (en) |
AU (1) | AU7684791A (en) |
BR (1) | BR9105168A (en) |
CA (1) | CA2056447A1 (en) |
OA (1) | OA09402A (en) |
WO (1) | WO1991014944A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994004078A1 (en) * | 1992-08-25 | 1994-03-03 | Epitope, Inc. | Oral collection device and kit |
US5714341A (en) * | 1994-03-30 | 1998-02-03 | Epitope, Inc. | Saliva assay method and device |
EP1380829A1 (en) * | 2001-04-20 | 2004-01-14 | Sapporo Immuno Diagnostic Laboratory | Instrument for use in collecting and recovering liquid secretion in oral cavity |
WO2006133392A1 (en) * | 2005-06-08 | 2006-12-14 | Vanderbilt University | Sampling of blood analytes |
CN111965277A (en) * | 2020-08-06 | 2020-11-20 | 天津科德通生物科技有限公司 | Automatic collection device for antibody purification effluent liquid |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0456794A1 (en) * | 1989-12-01 | 1991-11-21 | PB Diagnostic Systems, Inc. | Immunoassay for antibodies to infectious disease agents |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0200381A1 (en) * | 1985-04-04 | 1986-11-05 | Hybritech Incorporated | A solid phase system for use in ligand-receptor assays |
EP0264804A1 (en) * | 1986-10-23 | 1988-04-27 | BEHRINGWERKE Aktiengesellschaft | Bio-affined porous solid phases, process for the preparation of bio-affined porous solid phases and their use |
WO1989001527A1 (en) * | 1987-08-21 | 1989-02-23 | Cellular Products, Inc. | Test device and method of preparing same, assay kit and method for the simultaneous detection of two htlv or hiv antibodies |
-
1991
- 1991-03-27 WO PCT/NL1991/000051 patent/WO1991014944A1/en not_active Application Discontinuation
- 1991-03-27 AU AU76847/91A patent/AU7684791A/en not_active Abandoned
- 1991-03-27 CA CA002056447A patent/CA2056447A1/en not_active Abandoned
- 1991-03-27 BR BR919105168A patent/BR9105168A/en unknown
- 1991-03-27 EP EP91907904A patent/EP0474858A1/en not_active Withdrawn
- 1991-11-21 OA OA60099A patent/OA09402A/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0200381A1 (en) * | 1985-04-04 | 1986-11-05 | Hybritech Incorporated | A solid phase system for use in ligand-receptor assays |
EP0264804A1 (en) * | 1986-10-23 | 1988-04-27 | BEHRINGWERKE Aktiengesellschaft | Bio-affined porous solid phases, process for the preparation of bio-affined porous solid phases and their use |
WO1989001527A1 (en) * | 1987-08-21 | 1989-02-23 | Cellular Products, Inc. | Test device and method of preparing same, assay kit and method for the simultaneous detection of two htlv or hiv antibodies |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994004078A1 (en) * | 1992-08-25 | 1994-03-03 | Epitope, Inc. | Oral collection device and kit |
US5714341A (en) * | 1994-03-30 | 1998-02-03 | Epitope, Inc. | Saliva assay method and device |
EP1380829A1 (en) * | 2001-04-20 | 2004-01-14 | Sapporo Immuno Diagnostic Laboratory | Instrument for use in collecting and recovering liquid secretion in oral cavity |
EP1380829A4 (en) * | 2001-04-20 | 2009-12-30 | Sapporo Immuno Diagnostic Lab | Instrument for use in collecting and recovering liquid secretion in oral cavity |
WO2006133392A1 (en) * | 2005-06-08 | 2006-12-14 | Vanderbilt University | Sampling of blood analytes |
CN111965277A (en) * | 2020-08-06 | 2020-11-20 | 天津科德通生物科技有限公司 | Automatic collection device for antibody purification effluent liquid |
Also Published As
Publication number | Publication date |
---|---|
EP0474858A1 (en) | 1992-03-18 |
OA09402A (en) | 1992-09-15 |
AU7684791A (en) | 1991-10-21 |
CA2056447A1 (en) | 1991-09-29 |
BR9105168A (en) | 1992-08-04 |
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